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Description/Abstract

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and by the accumulation of ?-amyloid (A?) peptides insenile plaques and in the walls of cortical and leptomeningeal arteries as cerebral amyloid angiopathy (CAA). There also isa significant increase of interstitial fluid (ISF) in cerebral white matter (WM), the pathological basis of which is largelyunknown. We hypothesized that the accumulation of ISF in dilated periarterial spaces of the WM in AD correlates with theseverity of CAA, with the total A? load in the cortex and with Apo E genotype. A total of 24 AD brains and 17 nondementedage-matched control brains were examined. CAA was seen in vessels isolated from brain by using EDTA-SDS lysis stainedby Thioflavin-S. Total A? in gray matter and WM was quantified by immunoassay, ApoE genotyping by PCR, and dilatationof perivascular spaces in the WM was assessed by quantitative histology. The study showed that the frequency and severityof dilatation of perivascular spaces in the WM in AD were significantly greater than in controls (P < 0.001) and correlatedwith A? load in the cortex, with the severity of CAA, and with ApoE ?4 genotype. The results of this study suggest that dilationof perivascular spaces and failure of drainage of ISF from the WM in AD may be associated with the deposition of A? in theperivascular fluid drainage pathways of cortical and leptomeningeal arteries. This failure of fluid drainage has implicationsfor therapeutic strategies to treat Alzheimer’s disease.